FI108403B - Material suitable for tissue reconstruction in an individual - Google Patents

Description

108403

MATERIALS SUITABLE FOR INDIVIDUAL TISSUE RECONSTRUCTION

The invention relates to a material as defined in the preamble of claim 1 and to its use.

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BACKGROUND

The publications used to illustrate the background of the invention and the prior art, which are hereinafter referred to, are to be considered as included in the description of the invention below.

10 The term "tissue" is used herein to refer to both hard tissue (bone, tooth and cartilage) and soft tissue. The supporting tissue may be a hard tissue or a soft tissue structure such as a tendon, connective tissue, or ligament.

Materials which have been tried and used for the reconstruction of skeletal tissue, in particular bone tissue, include calcium-phosphate-based materials made from bovine bone, hydroxyapatite made by chemical processes, cadmium phosphate, tricalcium 20 bone tissue itself, either patient's own bone (autograph) or bank bone (allograft) (Aho & <* * «

Heikkilä 1997). All of these materials have some side effects, either because of the complex manufacturing process of the material, the unsatisfactory strength of the material, its difficult handling or unsatisfactory workability, or the potential risk of infectious diseases. 25 materials having no the above-mentioned negative properties have been applied for, and in addition

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in structure and elasticity would be similar to bone tissue and would be easy. processable. In particular, machinability refers to the shaping of a part, the sawing, carving and drilling of the material and the attachment of the part to the application. The workability of the above-mentioned known materials is unsatisfactory. In addition, they are fragile and susceptible to breakage.

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In 1997, an abstract published in the literature of an experiment on wood, or juniper, in rabbit bone (Gross et al., 1997). However, the juniper tree used in this experiment was not pre-treated in any way.

OBJECTIVE AND SUMMARY OF THE INVENTION It is an object of the present invention to provide a novel material suitable for tissue reconstruction of an individual, in particular for the reconstruction of a supporting tissue such as bone tissue 10.

In particular, it is intended to provide a material which permits the formation of new tissue within the material and / or favors tissue adhesion. to the surface of the material.

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It is also an object to provide a material which is compatible with the bioactive material, various active substances or agents that promote biodegradation.

The purpose is also to provide the material of which the piece is made. · High strength properties with good workability and yet structure that allows new tissue to be formed inside and / or attached to the body.

These objects are achieved by the material according to the invention, the features of which are disclosed in the claims.

The invention thus relates to a tissue-embedded material suitable for tissue reconstruction of an individual, in particular for support such as bone tissue, characterized in that it consists of wood which has been heat-treated at a temperature in the range of 100 to 220 ° C in the presence of water vapor.

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The invention also relates to the application of the new material to medical or dental, in particular surgical or therapeutic, objects, i.e. to repair various deficiencies of the supporting tissue, in particular bone or bone; as part of bone; nivelrustopintoina; as filler for bone cavities; pipe reconstruction; as a repair plate for the fundus or facial bones or as a filler for cavities; skull plate; a nail; a screw; vertebral column repair; luusementtikomponenttina; as a joint prosthesis or implant, either alone or in combination with metal prostheses, plates or implants; jaw-10 and / or dental implant; mineralizing toothpicks; The splint; periodontal filling; dental cements; surgical paste; as a tissue guiding film or tube; protective aprons; haavaliinana; in combination with autogenous or allogeneic bone; or as an ingredient in other biomaterial formulations such as plastics (e.g., acrylics) or various compositions.

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RECOMMENDED EMBODIMENTS AND DETAILED DESCRIPTION

The wood used in the present invention may be either hardwood or softwood. Deciduous trees are primarily birch, aspen, oak, alder, poplar, and softwoods include pine, juniper, spruce and larch.

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Making wood available for use in tissue requires sterilization, that is, elimination of bacteria, molds, fungi and spores. This is achieved by heat treating the wood in the temperature range of 100 to 220 ° C .. 25 in the presence of water vapor, thereby preventing the wood from burning. Heating * above 100 ° C alters the physical and chemical properties of wood. In a temperature range of 100 to 200 ° C, water is removed from the wood and the polymer chains of the carbohydrates are broken and free acids are formed. Carbohydrates continue to decompose and pyrolysis of lignin and wood begins (Pecina & Paprycki 1988). Thus, it is essential to partially disintegrate the major components of wood 4,108,403, i.e. cellulose, hemicellulose and lignin.

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Acetic acid produced by the degradation of cellulose and hemicellulose depolymerises microfibrils of cellulose. Hydrolysis of hemicellulose produces soluble sugars (Hillis 1984). Thermal treatment also produces polysaccharides by hot and cold water extraction (Fengell 1966). Deciduous pentosans are more susceptible to decomposition than softwood hexanes (Kollman & Fengell 1965), and the effect of heat treatment on different wood species depends on the type and amount of hemicellulose. Lignin is 10 heat resistant.

The wood material of the material of this invention is heat treated with moist air in the presence of water vapor (Viitaniemi & Jämsä 1996). This method is also described in the Finnish patent FT 103834. Such a method has also been used in the wood industry to improve the resistance of wood to decay. As a result of the heat treatment, the wood becomes darker in color, increases its resistance to decay and mildew, decreases its moisture content by 80 to 90% and its bending strength by 10 to 15%. Changes in the fiber structure of wood can be observed, e.g., longitudinal cracks in cell walls.

According to a suitable embodiment, during the heat treatment, the difference between the internal temperature of the wood piece and the temperature of the medium (air and water vapor) surrounding the wood piece is limited, preferably not more than about 30 ° C. In this way, it is ensured that cracks that weaken the strength do not occur to the wood material.

... 25 The water vapor used is suitably saturated water vapor.

The wood thus treated can be machined to the desired piece shape, allowing also drilling holes.

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Alternatively, the pieces of wood of the desired shape can be first processed and then heat treated.

In yet another alternative, the desired shape 5 can be produced by compressing together heat-treated wood particles, such as wood chips or wood powder, or elongated particles of wood fibers. Suitable additives for promoting the cohesiveness of the body, such as acrylic resin or other tissue adhesives, may optionally be used. The particle pressed piece is suitable for use in applications where the strengths are less critical. From the aforementioned elongated wood particles, pieces having the desired elasticity, tensile strength and plasticity can be extruded. By varying the size and shape of the particles, the above properties can be controlled to a great extent.

According to yet another alternative, wood particles can be used as such (i.e. without being compressed into pieces), e.g. as a filler for bone cavities.

The heat treatment of the wood can be carried out either in the form of a larger body or in the form of particles.

According to a highly preferred embodiment, a bioactive component is also added to the material of the invention. The addition of a bioactive component can enhance and accelerate the growth of the wood structure and the surrounding tissue (bone and / or connective tissue). The bioactive component may further exhibit one or more of the following properties: tissue-binding or tissue-mineralizing, biocompatible, biodegradable, or release (e.g., antimicrobial). The bioactive component may be bioactive glass, bioactive polymer, silica gel, e.g., xerogel, Ti gel, ceramic, glass ceramic, calcium phosphate, hydroxyapatite, coral, or allogeneic or autogenous bone, or a mixture of the above components (Aho 1993; Heikk 1993; 1995; Buchholz et al. 1987; LeGeros & LeGeros 1993; Kangasniemi 1993).

The bioactive component may exist in various forms such as ions, particles, granules, spheres, fibers, rods or membranes. Thus, the bioactive component may be incorporated into the wood material in various ways.

The combination of the bioactive component with the wood material can be accomplished in various ways. If the wood material is in particulate form, it can be mixed with 10 particle bioactive material. If desired, the mixture can be compressed into pieces. If the wood material is in the form of a solid wood body, the finely divided bioactive material can be introduced into the body by a stream of gas or liquid. Thus, pressurized precipitation (whereby fine powder is transported inside the wood body), various mineralization techniques (impregnation of solutions), etc. for example, the liquid stream may be in the form of a solution, colloidal solution such as a sol, suspension or emulsion. The bioactive component may also exist as a separate layer, for example as a coating or laminate, in relation to the shaped body of the wood material. A combination of all of the above 20 is also possible.

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Other physiologically beneficial agents may also be added to the wood material, either alone or in combination with the bioactive component described above. Such active ingredients include growth factors, proteins (e.g., Bone morphogenetic protein, BMP), drugs (e.g., antibiotics or cytostats), sugars, hormones (such as anabolically active hormones), enzymes, other organic substances such as collagen, hyaluronic acid and antioxidants. Further, genetic material can be used to treat wood material, e.g., by introducing a growth-enhancing gene (e.g., a viral gene). The nature of the additive '30 to be used will depend on the application, on medical grounds, for the purpose of improving and accelerating the growth of the tissue and of affecting a underlying disease such as cancerous tissue and / or inflammation.

/ - The plastic material may also be incorporated into the wood material in mass, soluble or thermoplastic form (eg lactide / caprolactone) which is impregnated into the woody structure of the wood in the above-mentioned ways.

If desired, to promote and accelerate the biodegradability of the wood material, such materials may also be added. By special chemical techniques, this wood material may be treated to be controlled to be degraded, whereby it may be completely replaced by the parent tissue, e.g. In addition, enzymes such as collagenases and proteases, cathepsin and streptokinase or domain or gene transfer methods may be mentioned from these types of agents.

The wood material may form a dense or to a varying degree a porous body, eg a prosthesis. It can be shaped according to its application to be rod, plate, membrane or spherical or corresponding to the required anatomical structure.

20 Wood materials can also be used to make coatings and films. The wood material may be <»· ♦ - meshy, filamentary or in particle form such as fiber, powder, granular chips, or shaped body such as sheet, tube, rod, nail or screw. It is intended to be used to repair the anatomical structure, but also to fix it itself or bone with a wooden nail or similar spike through a borehole. The structure of the invention may also, in its unitary form, include holes or channels corresponding to the osteon structure of the bone cortex, and may be tubular in macrostructure, i.e., hollow inside, e.g. corresponding to the core and general structure of the tubule. It can be a lamellar disk, smooth or modified. The product may be soft, elastic, brittle or hardened.

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The material to be fitted to the tissue must, of course, be sterile. Microbes in the wood die as a result of heat treatment, but final sterilization of the product, for example by heat or irradiation, is recommended.

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Among the fields of application of the material according to the invention are bone tissue and cartilage deficiencies. Practical items include bone cavity filler material, reconstruction of tubules or flat bones with plate clamp, core nail or screw, ocular / facial bone repair plate, 10 skull plate, spinal vertebra repair, bone cement component, joint prosthesis, or implant coating. Applications in the dental and jaw field include, for example, dental implant coating, jaw implant, bite rail, paradontal filling, mineralizing toothpick, paste or tooth segment, or surgical paste. Other applications include tissue guiding membrane 15 or tube, cellular tissue growth network, scaffold, sheath, wound dressing and co-application with autogenous or allogeneic bone and carrier of active ingredients such as drugs.

The material according to the invention is intended to be used in particular in the following conditions: 1) Defective states resulting from bone tumors or hip-knee replacement surgery, which are either cavities. deficient states comprising the cartilage of the bone head and joint, the segment of the tubular shaft or the longitudinal hemisphere (see Figures Figures 1, 2 and 3).

25 2) Bone deficiency conditions associated with various fractures in the tubular or flat bones or vertebrae, which would require therapeutic bone transplantation.

3) It may be possible to make a new type of joint prosthesis (hip, knee) from the material according to the invention (see figure, Fig. 4).

9 108403 4) Development and Late Damage to Bone and Other Supporting Tissue, Including Dental Medicine in Spinal Jaws and Joints and Teeth such as: • Congenital developmental anomalies and later life, e.g.

5 defects and bone defects due to inflammation, osteoporosis and osteopenia.

5) In dentistry, implant and prosthetic fixation, bone ridge cultivation and shaping, toothpick (mineralizing).

6) Wood-bone cell combination may replace the use of autograft or allograft.

A very specific application can be mentioned bone-loss states resulting from cancer surgery. A malignant or aggressive bone tumor in the tubular bone 15 may need to be treated by surgically removing that portion of the tubular bone, resulting in a large bone defect area, e.g., 10 to 15 cm long. This defective area may be replaced by a correspondingly shaped and sized piece of wood (which may also include other components such as a bioactive component and an active ingredient) placed at the defective site (e.g., femur or tibia). The piece 20 is fastened either by a surgical disc with screws or preferably by a core nail. The bone-joint function will then be maintained and bone tissue will be able to grow to the implant in question (see Figures, Figs. 1-4).

The behavior of the material of the invention in bone is described in more detail by the following 25 examples.

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EXAMPLE

Studies conducted on heat-treated wood (aspen, birch, pine) • y; 30 made conical or cylindrical (2.5 x 5 mm) implants placed in rabbit

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108403 ίο drill holes in the knee bump. Microscopic examination of the implant cavities at 4-8 weeks reveals that at several points the fibrous structure of the wood is in direct tissue contact with bone. The connective tissue formed in the peripheral areas of the cavities was also structurally linked together. Macrophages but no sphincter cells or lymphocytes are detected in the border 5 interface (interface), i.e. no actual immunogenic reaction is observed. Macroscopically, small pieces of wood were neat on the surface of the bone and cartilage without fluid collection.

At twenty weeks, bone was more abundant in the material, and small ductular islets of bone and osteoid tissue were seen in its ductal interior.

10 Heat-treated wood has the potential for growth of live bone adhering to the fibrous structure. Partial micro- and macroscopic similarity of the structure of wood and compact bone tissue contributes to this phenomenon. Namely, wood is identified as cylindrical structures located inside one another, which are wood cells that connect to each other in both longitudinal and transverse passageways.

Cylindrical, lamellar tubular structures of hydroxyapatite-collagen filaments are also found in compact bone, e.g., tubular bone or cortical bone.

The blood vessels are located in the middle of them and also in the transverse direction.

A bioactive component, such as bioactive glass, further facilitates and accelerates the growth of bone tissue by structural and chemical attachment to the implant.

The above embodiments are only examples of implementing the idea of the invention. It will be apparent to one skilled in the art that various embodiments of the invention may vary within the scope of the following claims.

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REFERENCES

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Aho A J, Heikkilä J T. Bone substitutions and related materials in clinical orthopedics. In: Advances in Tissue Banking, Vol. 1, eds Phillips G O, Versen R, 5 Strong M, Nather A. World Scientific, Singapore 1997: 73-107.

Aho A J, Heikkilä J T, Andesson Ö H, Yli-Urpo A. Morphology of osteogenesis in a bioactive glass interface. Ann Chirurg Gynaecol 1993; 82: 145-153.

10 Bucholz R W, Carlton A, Holmes R. Hydroxyapatite and tricalcium phosphate as bone graft substitutes. Orthop Clin North Am 1987; 18: 323-334.

Fengell D. Heiss- und Kaltwasserextrakte von thermisch behandeltem Fichtenholz. Holz Roh Werkst 1966; 24: 9-14.

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Gross, Ezerietis E, Gardovski J, Skudra M, Vetra J. Juniper Woods as an Alternative Implant Material. 13th Conference on Biomaterials. Göteborg, Sweden 4-7 Sep, 1997. P. 36.

20 Heikkilä J. Bioactive glass as a bone substitute in experimental and clinical bone defects. Thesis. Ann Univ Turkuensis Ser D Tom 240. Turku 1996.

Heikkilä J T, Aho A J, Aho H J, Yli-Urpo A, Happonen R-P. Bone formation in rabbit cancellous bone defects filled with bioactive glass granules. Acta Orthop 25 Scand 1995; 66: 463-467.

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Hillis W. High temperature and chemical effects on wood stability. Part 1: General considerations. Wood Sci Technol 1984; 18: 281-293.

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Kangasniemi IM O. Development of Ca, P -ceramic Containing Bioactive Glass Composites. Thesis. University of Leiden, The Netherlands 1993.

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Kollman F, Fengell D. A Holder for Chemistry of Holz 5 Durch Thermische Behandlung. Holz Roh Werkst 1965; 23: 461-468.

LeGeros R Z, LeGeros J P. Dense hydroxyapatite. In: An introduction to bioceramics, eds Hench L L, Wilson J, World Scientific, Singapore 1993: 139-180.

10 Pecina H, Paprzycki O. Wechselbeziehungen zwishen der Temperaturbehandlung des Holzes und seiner Benetzbarkeit. Holzforsch Holzverwert 1988; 40: 5-8.

Roffael E, Schaller K. Einfluss thermischer Behandlung auf Cellulose. Holz Roh Werkst 1971; 29: 275-278.

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Viitaniemi P, Jämsä S. Modification of wood by heat treatment. VTT Publications 814.

Espoo 1996.

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Claims (11)

13108403 1. Tissue-embedded material suitable for the reconstruction of an individual's tissue, in particular a supporting tissue, such as bone tissue, characterized in that it consists of wood which has been heat-treated in the temperature range of 100 to 220 ° C in the presence of water vapor. Material according to Claim 1, characterized in that the wood has been treated so that the difference between the internal temperature of the wood and the temperature of the medium surrounding the wood has been limited, preferably not more than about 30 ° C, and that the water vapor is saturated steam. Material according to claim 1 or 2, characterized in that it is a piece of wood, such as a sheet or a stick, wherein the shaping is carried out before or after the heat treatment of the wood. Material according to Claim 1 or 2, characterized in that it is formed into a desired body by compressing together wood particles, such as wood chips or powder, or elongated particles of wood fibers. 20 Material according to one of Claims 1 to 4, characterized in that it further comprises a bioactive component. Material according to Claim 5, characterized in that the bioactive component, in fine form, is introduced into a whole piece of wood by a stream of liquid or gas. Material according to claim 5, characterized in that the bioactive component present in particulate form is mixed with the wood material in particulate form 30, after which the mixture is compressed to the desired body. 14108403 Material according to claim 5, 6 or 7, characterized in that the material is shaped into a body and that the bioactive component is present in a layer separate from the body, for example as a coating or a laminate. Material according to any one of claims 5 to 8, characterized in that the bioactive component is a bioactive glass, a bioactive polymer, silica gel, Ti gel, ceramic, glass ceramic, calcium phosphate, hydroxyapatite, coral, or allogeneic or autogenous bone, mixture of components. Material according to one of the preceding claims, characterized in that it contains an active substance, such as a drug, e.g. an antibiotic or a cytostat; 15 growth factor; protein; sugar; hormone; the enzyme; collagen or an antioxidant or a controlled disintegrant, or a mixture of any of the above. Material according to one of Claims 1 to 10, characterized in that it comprises a material according to any one of claims 1 to 10. substance biodegradable. 108403